Unlike English that, שֶׁ־ is almost never optional; for example, "the reason (that) he came" is הסיבה שהוא בא, never *הסיבה הוא בא. This applies in both its conjunction and its pronoun uses (below).

שֶׁ־ is often used after a preposition, such that together they act as a conjunction; for example, English before corresponds to Hebrew לפני when it's a preposition, and to Hebrew לפני ש־ when it's a conjunction.

When writing with niqud, שֶׁ־ induces a dagesh forte (dot) in the following consonant, unless the consonant is one that does not take a dagesh (one of א,‎ ה,‎ ח, ‎ע, or ר), in which case it does not have this effect. (Unlike with other constructions that induce dagesh, this one does not undergo any vowel changes in the case that dagesh is impossible.) This applies in both its conjunction and its pronoun uses (below).

Although the current vowelization of this prefix (as a conjunction or a pronoun) is always שֶׁ־, there are a number of instances in older texts where a different vowel was used: שַׁ־ or שָׁ־.

In its use to introduce relative clauses, ש־ straddles the line between pronoun and conjunction, in that it does not always eliminate its corresponding pronoun within the relative clause. (In colloquial English, this can happen in certain edge cases, such as "the woman who I'm not sure if you've met her", where who is a relative pronoun and her is the corresponding internal pronoun; but in Hebrew, this is a standard and universal feature.) Specifically, when ש־ acts as the subject of a relative clause, the corresponding pronoun within the relative clause is suppressed (though there may well be a pronoun serving as a copula); when it acts as the object of a preposition in a relative clause, the corresponding pronoun within the relative clause is not suppressed; and when it acts as the direct object of a relative clause (and hence, in a sense, as the object of the preposition את ‎(et)), the corresponding pronoun is usually suppressed, but may appear in colloquial speech (though this is usually considered incorrect).

In many cases where English or colloquial Hebrew would use a relative clause, formal Hebrew instead uses the verb's present participle (which is the same as its present tense; Hebrew does not fully distinguish these). This is especially quite common in Jewish liturgical blessings.

In formal Hebrew, ש־ often introduces attributive prepositional phrases (in order to distinguish them from predicative ones).

In the Bible, ש־ is not usually used as a relative pronoun or relativizer; rather, אשר ‎(ashér) is used instead.